Co-occurrence of shedding Herpes Simplex Virus type-2 (HSV-2), Human Papilloma Virus (HPV) and Human Immunodeficiency Virus 1 (HIV-1) in the female genital tract among HIV-infected women

Introduction: Human Immunodeficiency Virus remains as one of the largest pandemics in the world, with the prevalence of more than 70% of HIV-infected individual reside in Sub-Saharan Africa. Moreover, other sexually transmitted viral infection such as Human Papillomavirus and Herpes Simplex Virus also show a high prevalence in Sub-Saharan Africa. Recent studies show the presence of other viral STI in the genital region may have increased HIV shedding in the genital region. However, it not clearly known if the presence of ART or HIV may affect the shedding of other viral STI in the genital region and if the combination of other viral STI treatment and ART is necessary to treat an individual with multiple STI infection. Methods: This is a secondary data analysis study, based on analysing the data collected from a single-site, double-blinded randomized control study (2-IUD study). The research site was the Gugulethu Community Health Centre, Cape Town, South Africa and samples were collected between 2014 and 2018. Analysis was conducted on genital tract specimens of study participants obtained via the Menstrual Cup (MC) and Endocervical Swabs (ECS), collected at baseline, 3 and 6 months’ follow up visit from randomly selected 52 ART-Naïve participants and 56 age-matched women from the ART-Using group of the primary study. Logistic regression models were constructed to measure the associations between possible risk factors and viral STIs. Results are presented as odds ratios (OR) with 95% confidence intervals (CI). Results: ART-Naïve women had higher rates of HIV shedding in the genital tract at each visit. However, more than half of women using ART, most of them virally suppressed, had detectable genital HIV at one or more visits. Most of the participants showed pre-exposure to HSV-2, but shedding of HSV-2 was substantially less common. HPV was detected in 72% of the participants, with no significant difference by ART status. Overall, 70.3% of samples had at least one viral pathogen detected - 60.4% among ART-Using women compared to 82.8% in ART-Naïve women (P<0.001). Compared to ART-Naïve women, ART-Using women were significantly less likely to have co-occurrence of viral shedding overall. However, ART-Using women with higher VL had levels of viral co-occurrence similar to those of ART-Naïve women. Conclusion: Our analysis demonstrated that the ART-Using women were less likely to shed HIV, HSV-2, HPV and viral STI co-infection in the genital tract compared to ART-Naïve women. This may be be driven by plasma VL levels where ART-Using women with lower VL are less likely to shed these viruses compared to women with elevated VL, including those not on ART

The development of penguinpox virus (PEPV) as a vaccine vector : transfer vector construction and rescue of virus growth in rabbit kidney cells (RK-13) by vaccinia virus K1

Includes bibliographical references (leaves 131-137).Of the many vaccine trials which have taken place, the most promising results have been obtained from the recent phase 3 clinical trial which tested the ability of a dual protein and Canarypox virus recombinant to protect humans against HIV-1 infections. Because poxviruses are being developed as vaccine vectors against a number of diseases, it is important to continue the search for novel poxvirus vectors, in particular, those that do not cross-neutralize one another. This thesis describes the preliminary work performed on the development of Penguinpox virus (PEPV) as a vaccine vector

Association Between Net Vertebral Artery Flow Volume and Non-AF Stroke: A Retrospective 2-Year Analysis

Objectives: Association between net vertebral artery flow volume (NVAFV) and stroke types remains unclear. We hypothesize NVAFV is low in patients with posterior circulation infarction (PCI) and an ideal cut-off value for discriminating PCI from anterior circulation infarction (ACI) and controls may be present.Materials and Methods: As study candidates, we retrospectively enrolled hospitalized patients with first-time non-AF stroke within 2-years period. Consecutive non-AF, non-stroke subjects were enrolled as the control group. We compared NVAFV values among the PCI, ACI, and control groups.Results: Overall, 866 candidates—213, 418, and 235 candidates in the PCI, ACI, and control groups, respectively—were enrolled. NVAFV (mean ± SD) values were 134.8 ± 52.7, 152.3 ± 59.2, and 172.0 ± 54.7 mL/min in the PCI, ACI, and control groups, respectively. Statistics revealed significant difference (p &lt; 0.001) among three groups. To use NVAFV as a diagnostic parameter, the AUC of any two groups should be between 0.58 and 0.69. Most (93.6%) of the controls had NVAFV above 100 mL/min. The odds ratio of any non-AF stroke is 3.48 if the NVAFV is below 100 mL/min.Conclusions: NVAFV is lowest in non-AF PCI group. Low NVAFV is associated with both non-AF ACI and PCI. No ideal cut-off value is available to discriminate PCI from other two conditions. We agree that an NVAFV of 100 mL/min is the lower limit of a normal value. Any value below 100 mL/min indicates high stroke risk and implies diffuse cerebral atherosclerosis and impaired cerebral perfusion

Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery

Introduction Abdominal surgery is probably associated with more likelihood to cause acute kidney injury (AKI). The aim of this study was to evaluate whether early or late start of renal replacement therapy (RRT) defined by simplified RIFLE (sRIFLE) classification in AKI patients after major abdominal surgery will affect outcome. Methods A multicenter prospective observational study based on the NSARF ( National Taiwan University Surgical ICU Associated Renal Failure) Study Group database. 98 patients (41 female, mean age 66.4 +/- 13.9 years) who underwent acute RRT according to local indications for post-major abdominal surgery AKI between 1 January, 2002 and 31 December, 2005 were enrolled The demographic data, comorbid diseases, types of surgery and RRT, as well as the indications for RRT were documented. The patients were divided into early dialysis (sRIFLE-0 or Risk) and late dialysis (LD, sRIFLE -Injury or Failure) groups. Then we measured and recorded patients' outcome including in-hospital mortality and RRT wean-off until 30 June, 2006. Results The in-hospital mortality was compared as endpoint. Fifty-seven patients (58.2%) died during hospitalization. LD (hazard ratio (HR) 1.846; P = 0.027), old age (HR 2.090; P = 0.010), cardiac failure (HR 4.620; P < 0.001), pre-RRT SOFA score (HR 1.152; P < 0.001) were independent indicators for in-hospital mortality. Conclusions The findings of this study support earlier initiation of acute RRT, and also underscore the importance of predicting prognoses of major abdominal surgical patients with AKI by using RIFLE classification

Enhanced phosphocholine metabolism is essential for terminal erythropoiesis

Red cells contain a unique constellation of membrane lipids. Although much is known about regulated protein expression, the regulation of lipid metabolism during erythropoiesis is poorly studied. Here, we show that transcription of PHOSPHO1, a phosphoethanolamine and phosphocholine phosphatase that mediates the hydrolysis of phosphocholine to choline, is strongly upregulated during the terminal stages of erythropoiesis of both human and mouse erythropoiesis, concomitant with increased catabolism of phosphatidylcholine (PC) and phosphocholine as shown by global lipidomic analyses of mouse and human terminal erythropoiesis. Depletion of PHOSPHO1 impaired differentiation of fetal mouse and human erythroblasts, and, in adult mice, depletion impaired phenylhydrazine-induced stress erythropoiesis. Loss of PHOSPHO1 also impaired phosphocholine catabolism in mouse fetal liver progenitors and resulted in accumulation of several lipids; adenosine triphosphate (ATP) production was reduced as a result of decreased oxidative phosphorylation. Glycolysis replaced oxidative phosphorylation in PHOSPHO1-knockout erythroblasts and the increased glycolysis was used for the production of serine or glycine. Our study elucidates the dynamic changes in lipid metabolism during terminal erythropoiesis and reveals the key roles of PC and phosphocholine metabolism in energy balance and amino acid supply.United States. Defense Advanced Research Projects Agency (Contract HR0011-14-2-0005)National Heart, Lung, and Blood Institute (Grant 2 P01 HL032262-25

72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study.

Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz group had a viral load of less than 50 copies per mL. Of 57 (21%) mothers with a severe adverse event, three (2%) in the dolutegravir group and five (4%) in the efavirenz group were related to the drug (dolutegravir drug-related events were one woman each with suicidal ideation, suicide attempt, herpes zoster meningitis; efavirenz drug-related events were one woman each with suicide attempt and liver cirrhosis, and three people with drug-induced liver injury). Of 136 (56%) infants in whom severe adverse events were recorded, none were related to the study drugs. In addition to the three infant HIV infections detected at birth in the dolutegravir group that have been previously reported, an additional transmission in the efavirenz group occurred during breastfeeding despite optimal maternal viral suppression and serial negative infant tests in the first year of life. Dolutegravir was safe and well tolerated, supporting updated WHO treatment recommendations in pregnant and breastfeeding women. Infant HIV transmissions can occur during breastfeeding despite persistently undetectable maternal viral load highlighting the need for continued infant testing

An experimental investigation of the dielectric properties of rocks

The objective of this research is to experimentally study the electrical response of rocks to changes in grain size, salinity of saturating fluid, and partial saturation. The use of electrical permittivity measurements has been proposed as a complement to resistivity measurements in formation evaluation. The combination of the two measurements has the potential to evaluate reservoir wettability, estimate pore size (or grain size), and estimate clay content. An Agilent 4192A LF Impedance Analyzer in combination with the Agilent 16451B Dielectric Test Fixture was used in conducting the dielectric measurements. Because complications arose with the electrodes in the original configuration of the fixture, five different methods were attempted to search for the most convenient, yet most accurate method. The method selected was a two-electrode method applied with silver plated electrodes. The powder is applied onto the electrode surfaces to reduce electrode polarization effects and to eliminate any chemical reactions of the electrode surfaces with the saturating fluid. Experiments were performed using different samples of various grain sizes fully saturated with de-ionized water. An increase in grain size causes the bulk conductivity and dielectric constant to decrease. The peak of the loss tangent decreases as the grain size increases. In experiments conducted with fully saturated Berea sandstone an increase in salinity causes both the conductivity and dielectric constant to increase. When plotting the reactance (out-of-phase electrical impedance) against frequency, a maximum is observed in the kHz to MHz frequency range. This maximum decreases in magnitude but increases in frequency when salinity increases. This change is a result of the double layer effect. Saturation profiles of drying samples were measured before making partial saturation dielectric measurements. CT (Computed Tomography) scans were used to analyze the saturation profile of the porous samples under drying conditions. The scans showed that the saturation profile of the disk shaped samples (Berea, Boise, and Texas Cream) were fairly uniform, suggesting a uniform electrical current distribution. In partially saturated cores, both the conductivity and dielectric constant decrease with decreasing saturation. The decrease in saturation also creates a second local maxima in a plot of reactance per unit length versus frequency. This new maxima increases in magnitude but decreases in frequency as saturation decreases. It is concluded that the effects of salinity of saturating fluid, partial saturation, and grain size of the porous medium cause changes in the dielectric measurements. The exact mechanism that caused these changes will require models that take into account the pore structure, clay content and grain size.Petroleum and Geosystems Engineerin

BDNF val66met polymorphism on functional mri during n-back working memory tasks

Val66Met polymorphism on the brain-derived neurotrophic factor (BDNF) gene is associated with hippocampal pathology and impaired episodic memory. However, the influence of this polymorphism on working memory (WM) performance and patterns of brain activation is controversial. This study investigated the effects of BDNF Val66Met polymorphism on functional magnetic resonance imaging (fMRI) during n-back WM tasks in healthy middle-Aged adults. A total of 110 participants without subjective or objective cognitive impairment underwent BDNF genotyping. Eleven Met allele carriers and 9 noncarriers underwent fMRI during WM tasks. The WM performance was similar between the 2 groups. Increased brain activation in response to increases inWMloadswas observed in both groups. The Met allele carrier group showed consistently lower brain activation in the right superior frontal gyrus (SFG) and themiddle occipital gyrus than that of the noncarrier group (P0.001). No brain region showed increased activation during WM tasks in the Met allele group. BDNF Val66Met polymorphism may affect the WM network. Met allele carriers have lower brain activation in the right SFG and middle occipital gyrus than do noncarriers during WM tasks. Defective development of theWMnetwork during brain maturation or differentiation is a possible mechanism. Additional studies with a larger sample and longer follow-up period are warranted